The interaction of thyroxine and triiodothyronine with phosphatidylcholine vesicles was studied by fluorescence polarization using probes inserted in the membrane. The results indicate that T4 and T3 penetrate into the center of the bilayer, and possibly alter the membrane fluidity. A theoretical analysis of the rate of release of thyroxine or triiodothyronine from the plasma transport proteins in comparison to the rates of metabolism of the hormones by hepatocytes indicates that TBG does not play a rate-limiting role in the entry of hormone into cells.